Eleftherios Diamandis

..CONCLUSIONS: hK4 is found primarily in prostate tissue and is secreted in seminal plasma. Its value as a novel prostatic biomarker needs to be defined further...

..High-throughput proteomic and pathway analysis of hippocampal tissue provides a valuable source of disease-related proteins and biomarker candidates, since it represents one of the earliest affected brain regions in AD...

..Please see related research article here http://www.biomedcentral.com/1741-7015/11/52...

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..Not only does it provide essential signals for cancer cell dedifferentiation, proliferation, and survival but it also facilitates cancer cell local invasion and metastatic phenomena. Mol Cancer Res; 10(11); 1403-18. ©2012 AACR...

..Herein, an overview of the varying tumor-host interactions that influence tumor behavior will be discussed, in addition to the recent efforts undertaken to target these interactions and their potential to revolutionize EOC patient care...

..I further provide examples of combinations of some known cancer biomarkers that can perform well in niche clinical applications, despite individually being not useful...

..abstract:..

..Current biomarkers suffer from a lack of tissue specificity, rendering them vulnerable to non-disease-specific increases. The present study details a strategy to rapidly identify tissue-specific proteins using bioinformatics...

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..In this review, we examine the diagnostic and prognostic value of the 15 human kallikrein genes and proteins. It is clear that at least a few members show promise of becoming novel cancer and other disease biomarkers...

..Before this technology is used clinically, it is important to understand its advantages and limitations. These are summarized, along with proposals, on how to proceed in the future...

..Here, we describe an update of the genomic organization of these families in human and mouse, and provide some thoughts for future research directions...

..Our preliminary studies indicate that hK11 may represent a diagnostic and prognostic biomarker for ovarian cancer. The aim of the present study was to examine the prognostic value of hK11 expression in ovarian tumors...

..Some of these enzymes can be measured in cerebrospinal fluid (CSF) by using ELISA-type methodologies...

..It is clear that the method needs to be externally and thoroughly validated before clinical implementation is warranted...

..Our objective was to validate the performance of three new candidate lung cancer biomarkers, pentraxin-3 (PTX3), human kallikrein 11 (KLK11), and progranulin...

..Hence, our findings provide more in-depth information regarding the molecular mechanisms underlying cardiac glycoside-induced cytotoxicity...

..In addition to their diagnostic/prognostic potential, kallikreins may also emerge as attractive targets for therapeutics...

..The new developments in science and technology suggest that we are yet to realize the best times of this exciting profession...

..This is the first reported immunological assay for hK11. Analysis of this biomarker in serum may aid in the diagnosis and monitoring of ovarian and prostatic carcinoma...

..Our aim was to examine the possible use of cerebrospinal fluid, blood and tissue, and human kallikrein 6 (hK6) concentration as a marker of AD...

..One new member is the KLK6 gene, encoding for human kallikrein 6 (hK6), which is also known as zyme/protease M/neurosin. In this paper, we describe development of antibodies and a sensitive immunofluorometric procedure for hK6 protein...

..Despite the voluminous literature on this biomarker, relatively few reports have addressed the issue of its physiological function and its connection to the pathogenesis and progression of prostate and other cancers...

..The discovery of new ovarian cancer biomarkers that are suitable for early disease diagnosis and prognosis may ultimately lead to improved patient management and outcomes...

..Additional tumor markers are needed for the early detection of clinically relevant CaP. Our objective was to perform a qualitative proteomic analysis of conditioned medium (CM) from the CaP cell line PC3(AR)(6)...

..We propose that the protein either is not synthesized efficiently or is degraded very quickly...

..The assay was then used to examine levels of KLK15 in tissues and biological fluids...

..These findings may have clinical implications for the management of cancer and other disorders in which KLK14 activity is elevated...

..CONCLUSIONS: This immunofluorometric assay for hK13 may be used to examine the value of hK13 as a disease biomarker and to further explore the physiologic and pathobiologic role of this enzyme in human disease...

..This assay can be used to explore the potential of hK8 as a marker of cancer or other conditions...

..Here we examine the clinical utility of multiple members of the kallikrein family of proteins in non-manipulative urinary biomarker testing...

..Prostate-specific antigen (PSA) testing is a significant advance for early diagnosis of patients with CaP...

..These results indicate that hK11 is a novel, independent marker of favorable prognosis in patients with ovarian cancer...

..Similar results were obtained for overall survival. CONCLUSIONS: KLK9 is a new potential independent marker of favorable prognosis in breast cancer...

..Our preliminary data indicate that hK5 is a potential biomarker in patients with ovarian and breast cancer...

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..We speculate that hK11, along with other kallikreins, proteases, and inhibitors, participates in a cascade enzymatic pathway responsible for semen liquefaction after ejaculation...

..CONCLUSIONS: hK7 is associated with other unfavorable characteristics of ovarian cancer, but it is not an independent prognosticator for ovarian cancer...

..Some variants show tissue-specific expression. The KLK15 splice variant appears to be a candidate biomarker for prostate cancer...

..001 and P = 0.014, respectively). These results indicate that hK8 is an independent marker of favorable prognosis in ovarian cancer...

..KLK15 is upregulated mainly by androgens and to a lesser extent by progestins. The purpose of this study was to examine the prognostic value of KLK15 in ovarian cancer tissues...

..These data suggest that hK8 protein is detectable in ovarian cancer tissue extracts, serum, and ascites fluid, indicating that it may serve as a new ovarian cancer marker...

..Our preliminary data indicate that hK14 is a potential biomarker for breast and ovarian cancers...

..Since KLK14 was found to be regulated by steroid hormones in prostate cancer cell lines, we hypothesized that it will be differentially expressed in prostate cancer tissues compared to their normal counterparts...

..Serum hK10 represents a novel biomarker for ovarian cancer. We conclude that preoperative serum hK10 concentration is a strong and independent unfavorable prognostic marker for ovarian cancer...

..43 and 0.53; P = .027 and .014). A weak negative correlation was found between KLK14 expression and serum CA-125. KLK14 is a new, independent, and favorable prognostic marker for ovarian cancer...

..We conclude that in-depth proteomic analysis of cell culture supernatants of ovarian cancer cell lines can identify potential ovarian cancer biomarkers that are worth further clinical validation...

..KLK10 is also upregulated in ovarian cancer. We thus hypothesized that the KLK10 gene may be a target for mutations in various cancers...

..4. Like KLK2 and KLK3, the KLK5 gene is regulated by steroid hormones in the BT-474 breast cancer cell line. We have previously shown that KLK5 is differentially expressed in ovarian and breast cancer...

..Our proteomics approach for discovering novel ovarian cancer biomarkers appears to be highly efficient because it was able to identify 25 known biomarkers and 52 new candidate biomarkers that warrant further validation...

..The synergistic effects between estrogens and androgens on estrogen-sensitive genes may have implications on the role of the kallikreins in associated risk of breast cancer and progression...

..Our aim was to examine how certain signal transduction pathways influence the regulation of hormone-dependent kallikrein (KLK) gene expression in androgen-sensitive breast cancer cell lines...

..Kallikrein expression may have some value for differentiating ovarian cancer from other types of cancer or from non-malignant diseases that lead to ascites accumulation...

..4. Hippostasin has two alternative splicing isoforms, known as the brain type and prostate type. We have previously reported that the prostate-type isoform is not expressed in human prostate cancer cell lines...

..KLK5-SV1 may have clinical utility in various malignancies and should be further explored as a potential new biomarker for prostate and ovarian cancer...

..CONCLUSIONS: This study describes the first ELISA-type immunoassay for hK7 protein quantification. hK7 is found many human tissues and in various biological fluids...

..Our objective was to develop a highly sensitive immunoassay for hK6 and use it to examine the levels of hK6 in brain tissue extracts from Alzheimer's disease patients and control subjects...

..Identification and reporting CDC is important for the establishment of treatment strategies and monitoring prognosis...

..The observation that KLKs could represent targets for miRNAs suggests a post-transcriptional regulatory mechanism with possible future therapeutic applications...

..297; p < 0.001). Our findings provide evidence for an association between hK5 and more aggressive forms of epithelial ovarian cancer...

..6). CONCLUSIONS: We conclude that higher KLK7 expression in ovarian cancer tissue is associated with poorer prognosis of ovarian cancer patients, especially those with lower grade disease and those who have been optimally debulked...

..It is essential that research groups, the industry, and physicians collaborate to conduct large prospective, multicenter clinical trials to validate and standardize this technology, for it to have real clinical impact...

..We examined the relationship between a mutant (T) for wild-type (C) allele substitution of the human kallikrein-2 gene (KLK2), circulating human kallikrein-2 (hK2) levels and prostate cancer risk...

..Given that other kallikreins are sequestered by serum protease inhibitors, we hypothesized that hK13 may also interact with similar inhibitors. Our objective was to identify serum protease inhibitors that interact with human hK13...

..In conclusion, the expression level of several seminal plasma KLKs correlates with liquefaction and viscosity indicators of semen quality and may aid in their differential diagnosis and etiology...

..Our results demonstrate the utility of this cell culture proteomics approach to identify secreted and shed proteins that are potentially useful as serological markers for lung cancer...

..Recently, it has been shown that CpG island hypermethylation of the KLK10 gene is responsible for the tumor-specific loss of KLK10 gene expression in certain breast cancer cell lines...

..Here, we report generation of antibodies against the full-length recombinant KLK12 (classical form) and the immunohistological localization of this KLK in normal and malignant prostate tissues...

..In this mini-review, we aim to describe these three techniques and provide their advantages and disadvantages. In addition, we aim to address some of the challenges of cancer immunomics...

..For example, hK6, 10 and 11 are promising serological markers for ovarian cancer diagnosis. KLK10 may act as a tumor suppressor. In addition to their diagnostic and prognostic values, kallikreins may also be good therapeutic targets...

..69). These preliminary data suggest that the hK11:total PSA ratio could be a useful tumor marker for CaP and could be combined with percentage of PSA to further reduce the number of unnecessary prostatic biopsies...

..We here review the evidence linking kallikreins and cancer and their applicability as novel biomarkers for cancer diagnosis and management...

..Several markers exhibited more intense expression in cancers than in normal organs. Further investigation is needed to demonstrate complementary expression of markers in serum...

..CONCLUSIONS: hK2/free PSA and IGF-1/free PSA ratios may be useful adjuncts in improving patient selection for prostate biopsy...

..007 and P =.002, respectively). CONCLUSION: These results indicate that hK13 is an independent marker of favorable prognosis in ovarian cancer...

..009), nodal status (P = 0.005), disease stage (P = 0.004), and distant metastases (P = 0.04). NAF PSA provides useful prognostic information which may assist with breast cancer treatment...

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..Human kallikrein 6 (hK6) is significantly increased in serum in many patients with ovarian cancer and may have a role in amyloid precursor processing and Alzheimer disease. The forms of hK6 in biological fluids are poorly characterized...

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..Of special interest is the potential role of kallikreins in the central nervous system. In addition, many kallikreins seem to be candidate tumor markers for many malignancies, especially those of endocrine-related organs...

..These data suggest that KLK7 gene expression may be used as a marker of unfavorable prognosis for breast cancer patients...

..We investigated the role of hK2 serum values for predicting pathological stage, grade and Gleason score...

..hK2 and PSA, and hK6 and hK10 are highly associated. Higher premenopausal PSA levels suggest the influence of ovarian steroids. PSA shows the most promise in aiding in the early detection of breast cancer...

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..The human kallikrein 11 (hK11) marker has been reported to have favorable predictive value for ovarian cancer, although, by itself, it may be inferior to CA 125...

..If successful, our research will contribute to the development of new prostatic biomarkers and possibly, to better diagnosis which may lead to better clinical outcomes and reduced healthcare costs. ..

..In this grant proposal, we describe further studies, which will examine in greater detail, the ability of a test for the amount of this protein in blood to correctly diagnose the presence of ovarian cancer. ..

..Relevance of this research to public health: By achieving early ovarian cancer diagnosis, it will be possible to reduce the burden of the disease by administration of effective treatment as early as possible. ..